Parkinsonian Dementias: PET Findings

Abstract

The etiology of cognitive decline in Lewy body parkinsonism, including Parkinson disease (PD), is not only multifactorial but also heterogeneous and likely related to cumulative and interactive effects between changes in neurotransmitter functions, proteinopathies (α-synuclein, β-amyloid, tau), neuroinflammation, and -, vascular-, metabolic-, and other changes. Glucose metabolic studies have shown mixed subcortical and cortical changes in Parkinson disease with dementia (PDD). For example, incident dementia in idiopathic PD is heralded by decreased metabolism of visual association (Brodmann area 18) and posterior cingulate cortices with additional involvement of the caudate nucleus. Subsequent progression to dementia is associated with mixed subcortical, especially thalamic, and widespread cortical changes that involve the mesiofrontal lobes also. Neurotransmitter-specific PET imaging shows early and prominent nigrostriatal dopaminergic losses in PD, with no major differences between PD and PDD. Therefore, caudate nucleus, limbic, and mesofrontal dopaminergic denervations do not appear alone sufficient for development of PDD. Cholinergic imaging studies have shown relatively mild losses in PD without dementia but more prominent decreases in PDD. This suggests significant cholinergic pathology underlying progressive cognitive decline in PD. Average dopaminergic and cholinergic denervation does not appear to differ between PDD and dementia with Lewy bodies (DLB), supporting the view that PDD and DLB lie on a common disease spectrum. In vivo PET imaging studies show variable β-amyloid binding in PDD with prevalence of pathologic amyloid deposition higher in DLB compared to PDD. However, despite the relatively lower binding levels compared to Alzheimer disease (AD), β-amyloid deposition contributes to cognitive impairment early in the course of cognitive decline in PD, suggesting a lower symptomatic threshold for amyloid deposition compared to normal aging and AD.